Abstract P664: Proteomic Profiling of African-Ancestry Adults Identifies Potential Novel Biomarkers of Vascular Aging
Authors: Rain Katz, Ryan Cvejkus, Bharat Thyagarajan, Jeffrey Carr, James G Terry, Sangeeta Nair, Victor Wheeler, Iva Miljkovic, Emma Barinas-Mitchell, Allison L Kuipers
Journal: Circulation (2023)

During the aging process, the vasculature undergoes pathologic changes which are strongly associated with hypertension and future cardiovascular disease (CVD) risk. Previous work to identify protein biomarkers of these subclinical vascular changes, which have largely focused on single proteins, has observed many associations in different populations. However, research in African-ancestry populations, who are at high risk for hypertensive CVD, is limited and may be biased by the existing research in Whites. Therefore, we used a proteomic approach to identify biomarkers of vascular aging as assessed by pulse-wave velocity (PWV) and abdominal aortic calcification (AAC). We included 346 African-ancestry men from the Tobago Health Study, a prospective cohort study of community-dwelling men aged ≥40 years residing on the Caribbean island of Tobago. These men were aged from 53-89 years old (mean ± SD = 63.4 ± 8.1 years) and were overweight on average (mean ± SD BMI = 27.7 ± 4.3kg/m2). 79.2% of men had hypertension, 24.6% had diabetes, and 5.9% were current smokers. We quantified protein expression using the Olink® Target 96 Cardiovascular III proteomics panel which includes 92 proteins with known association to human cardiovascular processes (CVDIII; Olink®, Waltham, MA). Brachial-ankle PWV (cm/s) was measured using an automated waveform analyzer. AAC was measured in the aorta at the iliac bifurcation via CT and scored using the Agatston method. Partial Spearman correlations were calculated to assess the relationship between each protein biomarker and both vascular aging outcomes adjusting for age, Olink® assay batch, height, weight, diabetes status, hypertension status, and current smoking. There were 13 and 5 proteins correlated with PWV and AAC, respectively (at P&lt;0.05). All correlations were in the direct direction of effect. Only one protein, cystatin B, was correlated with both PWV and AAC (r= 0.17 and 0.12, P=0.002 and 0.03; respectively). After applying false discovery rate adjustment for multiple comparisons, only fatty acid binding protein 4 (FABP4) and PWV remained significant (r=0.18, P=0.046). In general, proteins categorized by Olink® as belonging to the inflammatory pathway were most likely to be correlated with PWV; whereas, those in the hormone response pathway were most frequently correlated with AAC. Our results highlight that FABP4, a protein related to atherosclerosis via inflammation, may also be an important marker of arterial stiffening in these African-ancestry men. Additionally, we identified cystatin B, a member of the cathepsin protease pathway, as a strong correlate of both PWV and AAC, which may warrant further research into it as a novel biomarker of vascular aging and CVD in this high-risk population. In conclusion, proteomics may be an effective tool for evaluating and identifying novel markers of vascular aging and CVD in underrepresented populations.